Heterozygous premature termination in zinc-finger domain of Kruppel-like factor 2 gene associates with dysregulated immunity

Kruppel-like factor 2 (KLF2) is a transcription factor with significant roles in development, maturation, differentiation, and proliferation of several cell types. In immune cells, KLF2 regulates maturation and trafficking of lymphocytes and monocytes. KLF2 participates in regulation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) pathway. Although pulmonary arterial hypertension (PAH) related to KLF2 genetic variant has been suggested, genetic role of KLF2 associated with immune dysregulation has not been described. We identified a family whose members suffered from lymphopenia, autoimmunity, and malignancy. Whole exome sequencing revealed a KLF2 p.(Glu318Argfs*87) mutation disrupting the highly conserved zinc finger domain. We show a reduced amount of KLF2 protein, defective nuclear localization and altered protein-protein interactome. The phenotypically variable positive cases presented with B and T cell lymphopenia and abnormalities in B and T cell maturation including low naive T cell counts and low CD27(+)IgD(-)IgM(-) switched memory B cells. KLF2 target gene (CD62L) expression was affected. Although the percentage of (CD25(+)FOXP3(+), CD25(+)CD127(-)) regulatory T cells (Treg) was high, the naive Treg cells (CD45RA(+)) were absent. Serum IgG1 levels were low and findings in one case were consistent with common variable immunodeficiency (CVID). Transcription of NF-kappa beta pathway genes and p65/RelA phosphorylation were not significantly affected. Inflammasome activity, transcription of genes related with JAK/STAT pathway and interferon signature were also comparable to controls. Evidence of PAH was not found. In conclusion, KLF2 variant may be associated with familial immune dysregulation. Although the KLF2 deficient family members in our study suffered from lymphopenia, autoimmunity or malignancy, additional study cohorts are required to confirm our observations.Peer reviewe

Sustainability transformations in the large-scale tree plantation sector

Workshop reportThis report provides a summary of the session ‘Sustainability transformations in the large-scale tree plantation sector’, which was part of the Sustainability Science Days that were held on Thursday, May 9th – Friday, May 10th, 2019 (https://www.helsinki.fi/en/conferences/sustainability-science-days-2019). The conference, and indeed this session, was organized jointly by the Helsinki Institute of Sustainability Science (HELSUS) of the University of Helsinki, and Aalto Sustainability Hub (ASH) of Aalto University. The overarching title of the conference was “Making and taking use of sustainability science”. The thematic focus of the Days was on sustainable production and consumption, and on the usefulness of sustainability science for decision making on various arenas – the political sphere, private-sector, higher education institutions, and beyond

Systeemiäly!

Teoksessa esitellään ensimmäisen kerran Raimo P. Hämäläisen luoma uusi systeemiälyn käsite ja pohditaan sen ilmentymiä eri elävän elämän konteksteissa. Systeemiäly tarkoittaa älykästä toimintaa, joka hahmottaa vuorovaikutuksellisia takaisinkytkentojä sisältäviä kokonaisuuksia. Systeemialykäs henkilö huomioi luovasti ja tarkoituksenmukaisesti ympäristonsä, itsensä sekä vuorovaikutuskokonaisuuden, minkä nämä muodostavat. Hän osaa toimia siinä älykkäästi. uskomme, että systeemiäly on yksi inhimillisen toiminnallisen jarkevyyden peruskäsitteitä Sillä on luonnollisesti yhteytensä Peter Sengen ja muiden systeemiajattelun uranuurtajien oivalluksiin ja tuloksiin. Missa systeemiajattelu tarkastelee ja mallintaa vuorovaikutuksia ulkoapäin , siinä systeemiäly on toiminnallisessa tilanteessa ilmenevää aktiivista käytännöllistä järkeä. Uutta on systeemiälyn käsitteeseen sisältyvä toiminnallinen, henkilökohtainen ja elämänfilosofinen aines. Kirja ottaa ensimmäisä askeleita systeemiälyn käsiteen hahmottamisessa eri yhteyksissä